PubMed · 8595468
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J Orav. 1995. Sample selection.. https://pubmed.ncbi.nlm.nih.gov/8595468/
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A disease gene introduced into a rapidly growing population by a single individual remains in strong linkage disequilibrium with the surrounding molecular markers. Mapping strategies taking advantage of this phenomenon allow increased mapping resolution as compared to pedigree analysis. Demographic models underlying these strategies usually assume the population exponential growth approximated by Poisson distribution of the number of children per individual. Knowing the real demographic distribution in the studied French-Canadian population, we analyzed the validity of the Poisson approximation. We adapted the existing model of the Poisson branching process to the case of a rapidly growing population and to non-Poisson distributions. In consequence, we were able to apply maximum-likelihood methods to estimate the recombination rate under various demographic scenarios. Our analysis shows that the growth rate has a higher impact on the estimation of recombination rate than the shape of the demographic distribution. The choice of the demographic model (Poisson vs. non-Poisson) has little effect on the estimation of the recombination rate but affects the expected distribution of haplotype frequencies. This distribution, however, depends much more on the population growth rate. Finally, we also demonstrate the usefulness of the Luria-Delbrück method, which gives a correct estimation of the recombination rate in a growing population, provided the sampling error is taken into account in the confidence intervals.
A new similarity score (sigma-score) is proposed which is able to find the correct protein structure among the very close alternatives and to distinguish between correct and deliberately misfolded structures. This score is based on the general principle 'similar likes similar', and it favors hydrophobic and hydrophilic contacts, and disfavors hydrophobic-to-hydrophilic contacts in proteins. The values of sigma-scores calculated for the high-resolution protein structures from the representative set are compared with those of alternatives: (i) very close alternatives which are only slightly distorted by conformational energy minimization in vacuo; (ii) alternatives with subsequently growing distortions, generated by molecular dynamics simulations in vacuo; (iii) structures derived by molecular dynamics simulation in solvent at 300 K; (iv) deliberately misfolded protein models. In nearly all tested cases the similarity score can successfully distinguish between experimental structure and its alternatives, even if the root mean square displacement of all heavy atoms is less than 1 A. The confidence interval of the similarity score was estimated using the high-resolution X-ray structures of domain pairs related by non-crystallographic symmetry. The similarity score can be used for the evaluation of the general quality of the protein models, choosing the correct structures among the very close alternatives, characterization of models simulating folding/unfolding, etc.
Occupational diseases of dentists and dental nurses were compiled from the Finnish Register of Occupational Diseases. The cases were recorded during 3 3-year observation periods, namely 1982-1984, 1986-1988, and 1992-1994 (i.e., 9 observation years). The relative risk of developing occupational allergic contact dermatitis in different occupations was calculated from the statistics of the years 1986-1991, and was expressed as the age-standardized rate ratio (SRR). During the 9 observation years, the majority of registered occupational diseases of dentists and dental nurses were skin diseases (221/312; 70.8%), followed by occupational repetitive strain injuries (61/312; 19.6%) and occupational respiratory diseases (20/312; 6.4%). The incidence rate (IR) for allergic contact dermatoses/10,000 workers (contact urticaria included) increased from 26 (95% confidence interval (CI) 16-40) in 1982-1984 to 79 (95%, CI 64-97) in 1992-1994. The IR/10,000 of allergic contact dermatoses increased especially for dentists, from 5.4 (95% CI 0.7-19) in 1982 to 67 (95% CI 45-95) in 1992-1994. The increase of the IR/10,000 dental nurses was smaller: from 43 (95%, CI 26-66) in 1982-1984 to 87 (95% CI 67-111) in 1992-1994. There was no increase in the IR/10,000 cases of irritant dermatoses. The most common causes of allergic contact dermatitis were plastics, disinfectants and antimicrobials, rubber chemicals, and mercury/mercury salts. The most common causes of irritant contact dermatitis were detergents, wet and dirty work, plastic chemicals and antimicrobials. Currently, Finnish dentists have the highest risk and dental nurses have the 4th highest risk of any occupation for developing occupational allergic contact dermatitis: the risk was 6.4-fold (SRR 6.4) in dentists and 6.1-fold in dental nurses, as compared to the general working population. It is evident that safer acrylics and protective gloves, better product declarations and material safety data sheets, as well as more information about protective measures, including non-touch working techniques, are needed.